Fermentation process, ranging from the production of alcoholic beverages to the production of antibiotics have a long history during wich a mass of experimental studies and publications including both the results of such studies and theories as to the mechanisms involved have been produced. Theories, of course, are based on observation, and then are used as the basis for improving process conditions, the objective being to optimize the process so as to increase both the quality and the quantity of product. Further, it is an object to cut the costs of production, particularly so far as raw materials and the yield therefrom are concerned.
In general, control of process variables has been based on correlations established between selected values of process variables and the quantity and quality of product output. However, measurement of quantity and quality of output during the course of a process is a relatively slow procedure, so that using such a method, there is, of necessity, a substantial lag between sampling of the output and the effecting of a change in process variables to correct any deviation from optimum output. Moreover, the nature of the output will change during the course of a biosynthesis process so that the levels at which the process variables should be held will similarly change during the course of a process, such a situation being characteristic, particularly, of batch processes.
As a result of the time lag, as will be shown, biosynthesis processes have frequently been run under conditions which deviate substantially from optimum. Also, so-called "laws" have been formulated and "effects" have been discovered which have been proved to be erroneous. An excellent example of the latter is the so-called "Pasteur effect" which is concerned with the suppression of formation of alcohol during the growth of yeast in the presence of oxygen. It has been thought that production of ethyl alcohol, when yeast is the desired end product, will be suppressed if the oxygen feed rate is high and the concentration of fermentable carbohydrate in the culture is maintained at a low level. In fact, the so-called "Zulauf" process on which a number of patents has issued requires maintaining the carbohydrate level below 0.0004%. To keep the carbohydrate level this low, the molasses used as the nutrient must be added very slowly. Since the concentration of molasses is low, the process itself is necessarily slow. As a result, the rate of production of yeast is likewise slow. Accordingly, production rates of yeast or cell mass are in the range of 1.2 g/l hour. As will be shown, it is possible to suppress the formation of alcohol and yet achieve a much higher rate of production of cell mass by other means.
In view of the large number of variables involved in the usual biosynthesis process, the availability of small and relatively inexpensive calculators or microprocessors has generated great interest in applying such devices to the control of such processes. However, the combining of the microprocessor with appropriate sensors for determining the reaction conditions and then controlling process variables has not always been fully successful. A major reason, as is implied above, is that correlations between operating variables and product output have been sought as the basis for controlling the process. And, as aforenoted, substantial lags interfere with on-line, real time control. It will be shown intermediate quantities, i.e. quantities which can be calculated from measurements provided by sensors, and which can be correlated both with product output and with operating conditions provide a superior method of controlling biosynthesis processes.